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Redox signaling

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Redox refers to Reduction-Oxygenation. Some atoms and molecules, such as Hydrogen and Sodium tend to naturally and easily give up their electrons, or allow their electrons to shift farther away. These types of molecules that give up their electrons are called Reducers. Meanwhile, on the other side of the reaction, some atoms and molecules such as Oxygen, Chlorine and Fluorine tend to take electrons, or draw electrons closer towards themselves. These types of atoms and molecules are called Oxidizers, because they are an oxidizing agent. Since salt water is made up of a solution of sodium and chlorine and oxygen and hydrogen, salt water is naturally full of Redox chemicals.

Redox signaling is simply biochemical communication within the cells and body by free radicals, reactive oxygen species (chemically reactive molecules containing oxygen), and other electrochemically active species such as nitric oxide, acting as biological messengers. Arguably, hydrogen sulfide and carbon monoxide are also redox signaling molecules. Similarly, modulation of charge-transfer processes and electronic conduction in macromolecules is also redox signaling. For a review, see Forman.. There appear to be a large number of redox signaling molecules, and they are involved in many different processes. Some redox signaling molecules are as simple as hydrogen peroxide while others are much more complex chemicals and organic compounds. Redox signaling molecules are produced in every cell of living things. During the biological processes of life, including such essential processes as breathing oxygen, oxidative free radicals and other harmful compounds are generated and redox signaling is activated. Essentially, Redox signaling is one of the means by which the body controls certain potentially harmful chemicals, compounds, processes and injuries. For example, reactive oxygen species likely play a key role in fibrocyte activation and thus scar formation. These molecules act as messengers or triggers and are produced on demand, within the cells, as the cells need them. Redox signaling molecules are universally present in living tissue in response to cellular stresses and injury. Because redox signaling is a balancing process involved in homeostasis and is produced in the cells on an as needed basis, there currently is no scientific evidence of any beneficial effect from attempts to supply the body with external sources of redox signaling molecules.

History

In a series of papers beginning in 1941, Szent-Gyorgyi proposed that modulation of electronic processes in semiconductive macromolecules plays a key role in biological function and in diseases such as cancer. Hush reviews the history of such molecular electronics.

Similarly, the first modern statement of the "ROS are messengers" component of redox signaling appears to be that of Proctor,. At a 1979 congress of free radical investigators he further generalized this concept to suggest that " ....active oxygen metabolites act as specific intermediary transmitter substances for a variety of biological processes including inflammation, fibrosis, and possibly, neurotransmission.." and " One explanation for this data is that various active oxygen species ( or such products as hydroperoxides ) may act as specific transmitter substances....". This global concept was published in a 1984 review. The next reference seems to be Bochner and coworkers., reporting increased synthesis of "alarmome" adenylylated nucleotides as a specific response to oxidative stress in bacteria.

Electronic conduction in redox signaling

Hush credits Mcginness and coworkers . with the first experimental confirmation of Szent-Gyorgyi's theories concerning semiconductor mechanisms in cellular signaling. Priel and coworkers postulate active electrochemical mechanisms in modulation of cellular processes by microtubules. Bettinger and Bao review recent work on biomaterial-based organic electronic devices. Such may play a role in control of cellular function.

Reactive oxygen species as messengers

The formation of ROS such as hydrogen peroxide underlies much biotic and abiotic stress signaling. For example, as signaling molecules, hydrogen peroxide and other ROS post- translationally modify target proteins by oxidizing thiol groups, thus forming disulfide bonds that reversibly alter protein structure and function. Specificity is achieved by localized production, concatenate hormone or calcium signaling, with targeted secondary oxidation occurring via glutaredoxins or thioredoxins. Target proteins containing reduction-oxidation (redox) sensitive thiol groups include i) signal transduction pathway proteins, such as phosphatases and mitogen-activated protein kinases, ii) embryogenesis regulating proteins iii) many transcription factors, iv) RNA-binding proteins that direct DNA methylation, and v) proteins involved in histone acetylation, deacetylation or methylation.

Similarly, the tyrosine-specific Protein Tyrosine Phosphatases are intracellular activities lacking disulfide bonds, but they might sense intracellular redox potential through the conserved cysteine in their active sites An intracellular oscillation of oxidant levels has been experimentally linked to maintenance of the rate of cell proliferation.

As an example, when chelating redox-active iron is present in the endosomal/lysosomal compartment of cultured epithelial cell line HeLa with the iron chelator desferrioxamine, cell proliferation is inhibited.

Thioredoxin (Trx) signaling Is also important in Cancer, as are other aspects of redox signaling.

References

  1. Jerzy Bełtowski and Anna Jamroz-Wiśniewska, Modulation of H2S Metabolism by Statins: A New Aspect of Cardiovascular Pharmacology . Antioxidants & Redox Signaling. July 1, 2012, 17(1): 81-94. doi:10.1089/ars.2011.4358.
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  5. Szent-Gyorgyi, A., 1941b. The study of energy-levels in biochemistry. Nature 148 (3745), 157–159. Szent-Gyorgyi, A., 1957. Bioenergetics. Academic Press, New York. Szent-Gyorgyi, A., 1960. Introduction to a Submolecular Biology. Academic Press, New York. Szent-Gyorgyi, A., 1968. Bioelectronics. Academic Press, New York. Szent-Gyorgyi, A., 1976. Electronic Biology and Cancer. Marcel Dekker, Inc., New York. Szent-Gyorgyi, A., 1978. The Living State and Cancer. Marcel Dekker, Inc., New York.
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  21. "Tyrosine specific protein phosphatases at PROSITE"Template:Inconsistent citations{{cite web}}: CS1 maint: postscript (link)
  22. "Interpro record for Tyrosine specific protein phosphatases"Template:Inconsistent citations{{cite web}}: CS1 maint: postscript (link)
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Further reading

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